Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV

Clinical Infectious Diseases, August, 2021.

NWCS 447 investigated a possible biological mechanism that may be an underlying factor causing brain impairment in people who are aging with HIV. This mechanism is triggered by persistent activation of a particular type of immune cell and results in accumulation of citrate and succinate in blood, reflecting a shift in cellular metabolism that may adversely affect the nervous system. Researchers evaluated the hypothesis that this metabolic shift would be linked to reduced walking speed and poorer performance on tests of memory and thinking. To do so, they measured citrate and succinate along with walking speed and memory in participants in the ACTG HAILO study who generously donated their time and samples to enable the research. The study included 957 people living with HIV who ranged in age between 40–78 years. On average, those with higher citrate and succinate levels had slower walking speeds and poorer memory than those with lower levels. This was particularly true for participants older than 60 years. These results confirm the research hypothesis and suggest that this shift in metabolism may underpin age-related brain impairment. Medications, supplements, and other interventions that affect this metabolic shift may benefit walking speed, memory, and thinking in people living with HIV.

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